Cross-hemispheric communication: Insights on lateralized brain functions.

On the surface, the two hemispheres of vertebrate brains look almost perfectly symmetrical, but several motor, sensory, and cognitive systems show a deeply lateralized organization. Importantly, the two hemispheres are connected by various commissures, white matter tracts that cross the brain's midline and enable cross-hemispheric communication. Cross-hemispheric communication has been suggested to play an important role in the emergence of lateralized brain functions.

Chronic Ca imaging of cortical neurons with long-term expression of GCaMP-X.

Dynamic Ca signals reflect acute changes in membrane excitability, and also mediate signaling cascades in chronic processes. In both cases, chronic Ca imaging is often desired, but challenged by the cytotoxicity intrinsic to calmodulin (CaM)-based GCaMP, a series of genetically-encoded Ca indicators that have been widely applied. Here, we demonstrate the performance of GCaMP-X in chronic Ca imaging of cortical neurons, where GCaMP-X by design is to eliminate the unwanted interactions between the conventional GCaMP and endogenous (apo)CaM-binding proteins.

Lateralization of short-term memory in the frontal cortex.

Despite essentially symmetric structures in mammalian brains, the left and right hemispheres do not contribute equally to certain cognitive functions. How both hemispheres interact to cause this asymmetry remains unclear. Here, we study this question in the anterior lateral motor cortex (ALM) of mice performing five versions of a tactile-based decision-making task with a short-term memory (STM) component.

Sparse imaging and reconstruction tomography for high-speed high-resolution whole-brain imaging.

Understanding brain functions requires detailed knowledge of long-range connectivity through which different areas communicate. A key step toward illuminating the long-range structures is to image the whole brain at synaptic resolution to trace axonal arbors of individual neurons to their termini. However, high-resolution brain-wide imaging requires continuous imaging for many days to sample over 10 trillion voxels, even in the mouse brain.

An entorhinal-visual cortical circuit regulates depression-like behaviors.

Major depressive disorder is viewed as a 'circuitopathy'. The hippocampal-entorhinal network plays a pivotal role in regulation of depression, and its main sensory output, the visual cortex, is a promising target for stimulation therapy of depression. However, whether the entorhinal-visual cortical pathway mediates depression and the potential mechanism remains unknown.

Multi-Scale Light-Sheet Fluorescence Microscopy for Fast Whole Brain Imaging.

Whole-brain imaging has become an increasingly important approach to investigate neural structures, such as somata distribution, dendritic morphology, and axonal projection patterns. Different structures require whole-brain imaging at different resolutions. Thus, it is highly desirable to perform whole-brain imaging at multiple scales.

A cortico-basal ganglia-thalamo-cortical channel underlying short-term memory.

Persistent activity underlying short-term memory encodes sensory information or instructs specific future movement and, consequently, has a crucial role in cognition. Despite extensive study, how the same set of neurons respond differentially to form selective persistent activity remains unknown. Here, we report that the cortico-basal ganglia-thalamo-cortical (CBTC) circuit supports the formation of selective persistent activity in mice.

Prolonged chronic social defeat stress promotes less resilience and higher uniformity in depression-like behaviors in adult male mice.

Chronic social defeat stress (CSDS) is widely applied to study of depression in rodents. 10-day CSDS was a most commonly employed paradigm but with high resilience ratio (∼30%), producing potential variation in depression-like behavioral symptoms. Whether prolonged period (21 days) of CSDS would promote less resilience and reduce behavioral variability remains unknown.

Mapping Functional Connectivity from the Dorsal Cortex to the Thalamus.

Neural activity in the corticothalamic network is crucial for sensation, memory, decision, and action. Nevertheless, a systematic characterization of corticothalamic functional connectivity has not been achieved. Here, we developed a high throughput method to systematically map functional connections from the dorsal cortex to the thalamus in awake mice by combing optogenetic inactivation with multi-channel recording.

Spatiotemporal constraints on optogenetic inactivation in cortical circuits.

Optogenetics allows manipulations of genetically and spatially defined neuronal populations with excellent temporal control. However, neurons are coupled with other neurons over multiple length scales, and the effects of localized manipulations thus spread beyond the targeted neurons. We benchmarked several optogenetic methods to inactivate small regions of neocortex.

Maintenance of persistent activity in a frontal thalamocortical loop.

Persistent neural activity maintains information that connects past and future events. Models of persistent activity often invoke reverberations within local cortical circuits, but long-range circuits could also contribute. Neurons in the mouse anterior lateral motor cortex (ALM) have been shown to have selective persistent activity that instructs future actions.

A motor cortex circuit for motor planning and movement.

Activity in motor cortex predicts specific movements seconds before they occur, but how this preparatory activity relates to upcoming movements is obscure. We dissected the conversion of preparatory activity to movement within a structured motor cortex circuit. An anterior lateral region of the mouse cortex (a possible homologue of premotor cortex in primates) contains equal proportions of intermingled neurons predicting ipsi- or contralateral movements, yet unilateral inactivation of this cortical region during movement planning disrupts contralateral movements.

Flow of cortical activity underlying a tactile decision in mice.

Perceptual decisions involve distributed cortical activity. Does information flow sequentially from one cortical area to another, or do networks of interconnected areas contribute at the same time? Here we delineate when and how activity in specific areas drives a whisker-based decision in mice. A short-term memory component temporally separated tactile "sensation" and "action" (licking).

Neural coding during active somatosensation revealed using illusory touch.

Active sensation requires the convergence of external stimuli with representations of body movements. We used mouse behavior, electrophysiology and optogenetics to dissect the temporal interactions among whisker movement, neural activity and sensation of touch. We photostimulated layer 4 activity in single barrels in a closed loop with whisking.

Controlling interneuron activity in Caenorhabditis elegans to evoke chemotactic behaviour.

Animals locate and track chemoattractive gradients in the environment to find food. With its small nervous system, Caenorhabditis elegans is a good model system in which to understand how the dynamics of neural activity control this search behaviour. Extensive work on the nematode has identified the neurons that are necessary for the different locomotory behaviours underlying chemotaxis through the use of laser ablation, activity recording in immobilized animals and the study of mutants.

Optical interrogation of neural circuits in Caenorhabditis elegans.

The nematode Caenorhabditis elegans has a compact nervous system with only 302 neurons. Whereas most of the synaptic connections between these neurons have been identified by electron microscopy serial reconstructions, functional connections have been inferred between only a few neurons through combinations of electrophysiology, cell ablation, in vivo calcium imaging and genetic analysis. To map functional connections between neurons, we combined in vivo optical stimulation with simultaneous calcium imaging.